Publications

Sokolovskiy A, Shah J, Collman S. Space Radiation Effects on Surface and Bulk Resistivity of Polymeric Materials. The Journal of the Astronautical Sciences. 2023;70;41.

Influence of accelerated electrons, solar vacuum ultraviolet, and atomic oxygen on the electrical properties of various types of polymeric materials of spacecraft external surfaces is investigated. It is shown that upon irradiation by 95 keV electrons with fluence of 5 × 1012 cm−2 and solar quanta with a dose of 1500 equivalent sun hours, the volume electrical resistivity does not change or changes by no more than one order of magnitude for some types of the polymeric materials. Irradiation with atomic oxygen with an energy of ~ 5 eV does not lead to a change in bulk resistivity of materials, while the surface resistivity alters depending on the type of polymer. It has been established that isothermal heating in a vacuum of non-irradiated and irradiated with atomic oxygen polymeric materials for a long time leads to the appearance of maxima in the kinetic curves of changes in surface resistivity. A physical model is proposed based on the assumption that at least two processes associated with the evaporation and diffusion of sorbed water molecules or hydroxyl groups into the near-surface layers of polymers are involved in the formation of such maxima.

Westrick S, Lambrecht S, Sokolovskiy A, Collman S, Shah J, Hoffman R, Engelhart D. Influence of High-Energy Electron Bombardment on the Material Properties of Spacecraft Polymers. The Journal of the Astronautical Sciences. 2023;70:40.

The interaction between the materials on the surface of a spacecraft and the space environment can lead to mechanical, chemical, and optical changes that affect their properties. It is crucial to comprehend how these materials respond to the different aspects of the space environment once they are in orbit and how these properties change over time. This knowledge is critical for predicting the spacecraft’s performance throughout its mission, ensuring its optimal functionality, and prolonging its lifespan. Selected polymers proposed for space applications were exposed to 95 keV electrons to simulate electron irradiation that the materials would receive in a range of different space environments. To assess the impact of electron irradiation on materials, reflectance spectra of both pristine and electron-irradiated samples were obtained and analyzed for changes in the Urbach edge. A change in the Urbach edge indicates changes in the material’s electronic structure, which can affect its electrical properties. Therefore, analyzing changes in the Urbach edge of irradiated materials can provide insight into their potential impact on the electrical conductivity of the material.

Ha, P., Kwak, J.H., Zhang, Y. et al. Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice. npj Microgravity 9, 75 (2023).

Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in longduration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke).

Parafati, M., Giza, S., Shenoy, T.S. et al. Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight. npj Microgravity 9, 77 (2023).

Microphysiological systems provide the opportunity to model accelerated changes at the human tissue level in the extreme space environment. Spaceflight-induced muscle atrophy experienced by astronauts shares similar physiological changes to muscle wasting in older adults, known as sarcopenia. These shared attributes provide a rationale for investigating molecular changes in muscle cells exposed to spaceflight that may mimic the underlying pathophysiology of sarcopenia. We report the results from three-dimensional myobundles derived from muscle biopsies from young and older adults, integrated into an autonomous CubeLab™, and flown to the International Space Station (ISS) aboard SpaceX CRS-21 as part of the NIH/NASA funded Tissue Chips in Space program. Global transcriptomic RNA-Seq analyses comparing the myobundles in space and on the ground revealed downregulation of shared transcripts related to myoblast proliferation and muscle differentiation. The analyses also revealed downregulated differentially expressed gene pathways related to muscle metabolism unique to myobundles derived from the older cohort exposed to the space environment compared to ground controls. Gene classes related to inflammatory pathways were downregulated in flight samples cultured from the younger cohort compared to ground controls. Our muscle tissue chip platform provides an approach to studying the cell autonomous effects of spaceflight on muscle cell biology that may not be appreciated on the whole organ or organism level and sets the stage for continued data collection from muscle tissue chip experimentation in microgravity. We also report on the challenges and opportunities for conducting autonomous tissue-on-chip CubeLabTM payloads on the ISS.

Dunkel, Emily R., Jason Swope, Alberto Candela, Lauren West, Steve A. Chien, Zaid Towfic, and others, ‘Benchmarking Deep Learning Models on Myriad and Snapdragon Processors for Space Applications’, Journal of Aerospace Information Systems, 0.0 (2023), 1–15.

Future space missions can benefit from processing imagery on board to detect science events, create insights, and respond autonomously. One of the challenges to this mission concept is that traditional space flight computing has limited capabilities because it is derived from much older computing to ensure reliable performance in the extreme environments of space: particularly radiation. Modern commercial-off-the-shelf processors, such as the Movidius Myriad X and the Qualcomm Snapdragon, provide significant improvements in small size, weight, and power packaging; and they offer direct hardware acceleration for deep neural networks, although these processors are not radiation hardened. We deploy neural network models on these processors hosted by Hewlett Packard Enterprise’s Spaceborne Computer-2 on board the International Space Station (ISS). We find that the Myriad and Snapdragon digital signal processors (DSP)/artificial intelligence processors (AIP) provide speed improvement over the Snapdragon CPU in all cases except single-pixel networks (typically greater than 10 times for DSP/AIP). In addition, the discrepancy introduced through quantization and porting of our Jet Propulsion Laboratory models was usually quite low (less than 5%). Models were run multiple times, and memory checkers were deployed to test for radiation effects. To date, we have found no difference in output between ground and ISS runs, and no memory checker errors.

McMackin PM, Adam JA, Riley FP, Hirsa AH. Single-camera PTV within interfacially sheared drops in microgravity. Experiments in Fluids. 2023;64:154.

Development of experimental methods for in situ particle tracking velocimetry (PTV) is fundamental for allowing measurement of moving systems non-tailored for velocimetry. This investigation focuses on the development of a post-processing methodology for single-camera PTV, without laser-sheet illumination, tracking native air bubbles as tracer particles within a liquid drop of human insulin in microgravity. Human insulin functioned as a sufficiently complex, non-Newtonian fluid system for testing fluid measurement methodology. The PTV scenario was facilitated by microgravity technology known as the ring-sheared drop (RSD), aboard the International Space Station, which produced an optical imaging scenario and fluid flow geometry suitable as a testbed for PTV research. The post-processing methodology performed included five steps: (i) physical system characterization and native air bubble tracer identification, (ii) image projection and single-camera calibration, (iii) depth determination and 3D particle position determination, (iv) ray tracing and refraction correction, and (v) particle history and data expansion for suboptimal particles. Overall, this post-processing methodology successfully allowed for a total of 1085 particle measurements in a scenario where none were previously possible. Such post-processing methodologies have promise for application to other in situ PTV scenarios allowing better understanding of physical systems whose flow is difficult to measure and/or where PTV-specific optical elements (such as laser light sheets and dual-camera setups) are not permissible due to physical or safety constraints.

Nagri, Shreya and Rice, Olivia and Chen, Yupeng "Nanomedicine strategies for central nervous system (CNS) diseases" Frontiers in Biomaterials Science , v.2 , 2023

The blood-brain barrier (BBB) is a crucial part of brain anatomy as it is a specialized, protective barrier that ensures proper nutrient transport to the brain, ultimately leading to regulating proper brain function. However, it presents a major challenge in delivering pharmaceuticals to treat central nervous system (CNS) diseases due to this selectivity. A variety of different vehicles have been designed to deliver drugs across this barrier to treat neurodegenerative diseases, greatly impacting the patient’s quality of life. The two main types of vehicles used to cross the BBB are polymers and liposomes, which both encapsulate pharmaceuticals to allow them to transcytose the cells of the BBB. For Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and glioblastoma brain cancer, there are a variety of different nanoparticle treatments in development that increase the bioavailability and targeting ability of existing drugs or new drug targets to decrease symptoms of these diseases. Through these systems, nanomedicine offers a new way to target specific tissues, especially for the CNS, and treat diseases without the systemic toxicity that often comes with medications used currently.

Yau, Anne and Jogdand, Aditi and Chen, Yupeng "Blood-brain-barrier modeling with tissue chips for research applications in space and on Earth" Frontiers in Space Technologies , v.4 , 2023

Tissue chip technology has revolutionized biomedical applications and the medical science field for the past few decades. Currently, tissue chips are one of the most powerful research tools aiding in in vitro work to accurately predict the outcome of studies when compared to monolayer two-dimensional (2D) cell cultures. While 2D cell cultures held prominence for a long time, their lack of biomimicry has resulted in a transition to 3D cell cultures, including tissue chips technology, to overcome the discrepancies often seen in in vitro studies. Due to their wide range of applications, different organ systems have been studied over the years, one of which is the blood brain barrier (BBB) which is discussed in this review. The BBB is an incredible protective unit of the body, keeping out pathogens from entering the brain through vasculature. However, there are some microbes and certain diseases that disrupt the function of this barrier which can lead to detrimental outcomes. Over the past few years, various designs of the BBB have been proposed and modeled to study drug delivery and disease modeling on Earth. More recently, researchers have started to utilize tissue chips in space to study the effects of microgravity on human health. BBB tissue chips in space can be a tool to understand function mechanisms and therapeutics. This review addresses the limitations of monolayer cell culture which could be overcome with utilizing tissue chips technology. Current BBB models on Earth and how they are fabricated as well as what influences the BBB cell culture in tissue chips are discussed. Then, this article reviews how application of these technologies together with incorporating biosensors in space would be beneficial to help in predicting a more accurate physiological response in specific tissue or organ chips. Finally, the current platforms used in space and some solutions to overcome some shortcomings for future BBB tissue chip research are also discussed.

Sapowadia, Avin and Ghanbariamin, Delaram and Zhou, Libo and Zhou, Qifa and Schmidt, Tannin and Tamayol, Ali and Chen, Yupeng "Biomaterial Drug Delivery Systems for Prominent Ocular Diseases" Pharmaceutics , v.15 , 2023

Ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, have had a profound impact on millions of patients. In the past couple of decades, these diseases have been treated using conventional techniques but have also presented certain challenges and limitations that affect patient experience and outcomes. To address this, biomaterials have been used for ocular drug delivery, and a wide range of systems have been developed. This review will discuss some of the major classes and examples of biomaterials used for the treatment of prominent ocular diseases, including ocular implants (biodegradable and non-biodegradable), nanocarriers (hydrogels, liposomes, nanomicelles, DNA-inspired nanoparticles, and dendrimers), microneedles, and drugloaded contact lenses. We will also discuss the advantages of these biomaterials over conventional approaches with support from the results of clinical trials that demonstrate their efficacy.

Sridhar K, Narayanan V, Bhavnani S. Asymmetric Sawtooth and Cavity-Enhanced Nucleation-Driven Transport (ASCENT) Experiment aboard the International Space Station – Microgravity Outcomes. 2023 22nd IEEE Intersociety Conference on Thermal and Thermomechanical Phenomena in Electronic Systems (ITherm). 2023;22:1-7.

Several forces exert an influence on two-phase bubble dynamics under terrestrial conditions, chief among these being those due to buoyancy and surface tension. Under microgravity conditions, the absence of buoyancy forces disrupts bubble dynamics preventing bubbles from detaching from surfaces. The stagnant bubbles form a large vapor mass attached to the surface, leading to a considerable rise in surface temperature. In this study, a mesoscale-engineered surface in the form of saw-toothed structures has been produced that can provide access to liquid pockets across the troughs of the microstructure in microgravity and terrestrial adverse-gravity orientation. The surface is built with intentional nucleation sites that support consistent vapor germination in both environments. Following terrestrial studies on various surface morphologies and under varying degrees of sub cooling, experiments were conducted onboard the International Space Station. The test chambers were square cross-sectioned glass ampoules with deposited thin film nichrome heaters. NASA's implementation partner developed the test and instrumentation hardware to conform to stringent flight requirements. The experimental investigation is titled Asymmetric Sawtooth and Cavity-Enhanced Nucleation-driven Transport (ASCENT) and was conducted in the Pore Formation and Mobility Investigation (PFMI) furnace. The paper discusses high- speed data obtained on vapor motion in microgravity and terrestrial downward-facing environments, providing insight into the differences between a flat surface and the microstructure. The images suggest the existence of a mobility diameter in microgravity, which enables favorable motion across the microstructure in both lateral directions. This mobility contrasts the slug mobility actuated by the sawtooth in the downward-facing terrestrial heater, where changes in the interfacial radius of curvature produce a net lateral motion in the direction of the long slope.

Alon, Dan Mark, Karin Mittelman, Eytan Stibbe, Stefanie Countryman, Louis Stodieck, Shankini Doraisingam, and others, ‘CRISPR-Based Genetic Diagnostics in Microgravity’, Biosensors and Bioelectronics, 237 (2023), 115479.

Monitoring astronauts' health during space missions poses many challenges, including rapid assessment of crew health conditions. Sensitive genetic diagnostics are crucial for examining crew members and the spacecraft environment. CRISPR-Cas12a, coupled with isothermal amplification, has proven to be a promising biosensing system for rapid, on-site detection of genomic targets. However, the efficiency and sensitivity of CRISPR-based diagnostics have never been tested in microgravity. We tested the use of recombinase polymerase amplification (RPA) coupled with the collateral cleavage activity of Cas12a for genetic diagnostics onboard the International Space Station. We explored the detection sensitivity of amplified and unamplified target DNA. By coupling RPA with Cas12a, we identified targets in attomolar concentrations. We further assessed the reactions' stability following long-term storage. Our results demonstrate that CRISPR-based detection is a powerful tool for on-site genetic diagnostics in microgravity, and can be further utilized for long-term space endeavors to improve astronauts' health and well-being.

Kober UA, Ogbuoji EA, Hutchinson JA, et al. Equilibration of precipitants in a counter-diffusion apparatus for protein crystallization. J Appl Crystallogr. 2023;56(4):1-9. DOI: 10.1107/S1600576723004958

A cost-effective capillary dialysis apparatus (Toledo Capillary Box, TCB) developed for biomacromolecule crystal growth in microgravity and unit gravity environments can provide slow equilibration between the precipitant reservoir and capillary solutions, nurturing growth of neutron-diffraction-quality crystals. Under microgravity conditions, mass transfer of precipitants and biomacromolecules occurs under diffusion-controlled conditions, promoting slow growth and suppressing defect formation. The equilibration of common precipitants (polyethylene glycol and salts such as ammonium sulfate) between capillary and reservoir solutions was measured for capillaries oriented horizontally or vertically with respect to the gravitational field at unit gravity. Precipitants equilibrated less rapidly in the vertical orientation when capillary solution densities were lower than those of the reservoir solutions. A plug filled with agarose gel was introduced in the TCB apparatus for salt precipitants since salts often exhibit relatively high free diffusion. Equilibration of the capillaries with reservoir solutions was significantly delayed for many of the salt precipitants tested. Analytical and semi-analytical models allow the prediction of precipitant equilibration of capillary and reservoir solutions under diffusion-controlled transport and show good agreement with experimental results.

Waddell KA, Lee HJ, Nayagam V, Axelbaum RL, Sunderland PB. Cool diffusion flames in a stably stratified stagnation flow. Combust. Flame. 2023;254:112852. doi:10.1016/j.combustflame.2023.112852

Cool diffusion flames have been a growing research topic since their discovery in 2012. Until now their study has been hindered by the high cost of the experimental systems used to observe them. A method is presented here for observing cool diffusion flames inexpensively using a pool of liquid n-heptane and parallel plates heated so as to produce a stably stratified stagnation flow. The flames were imaged with a color camera and an intensified camera. Measurements included gas phase temperatures, fuel evaporation rates, and formaldehyde yields. These are the first observations of cool flames burning near the surfaces of fuel pools. The measured peak temperatures were between 705 and 760 K and were 70 K above the temperature of the surrounding air. Autoignition first occurred at 550 K.

Cho YJ, Lu K. A materials informatics approach for composition and property prediction of polymer-derived silicon oxycarbides. Materials Today Advances. 2023;18:100384.

Polymer-derived silicon oxycarbide (SiOC) materials enable the formation of homogeneous microstructures and high temperature stable properties. However, the relationships between the processing parameters and microstructures/properties have not been clearly understood. In this study, a materials informatics approach was employed to the SiOC materials to analyze and estimate the relationships. Datasets were constructed from results of previously reported literature about SiOC. The correlation analysis provided processing parameter ranking regarding the corresponding influences on the properties and microstructures. Such an understanding can be utilized for desired material fabrication. Machine learning models with high accuracy were proposed using the ranked features obtained from the correlation analysis. In addition, important points on the data collection, correlation analysis, and machine learning as well as limitations of the current dataset were discussed. The proposed workflow for the SiOC materials can be extended to different types of polymer-derived ceramics by incorporating various features and targets involved in the processing variables, microstructures, and properties.

Chaney H, Lu K. ReaxFF Simulation of Pyrolysis Behaviors of Polysiloxane Precursors with Different Carbon Content. Chemistry of Materials. 2023;35:3902-3910.

Polymer-derived ceramics are a promising class of high-temperature materials. This work uses LAMMPS and reactive force field (ReaxFF) energy potential to first-time quantify the atomic evolution of the polymer-to-ceramic conversion. Three different polymer structures are selected based on initial carbon content and molecular structure differences. From these simulations, the ceramic composition, yield, atomic structure, bond change, and radial distribution function (RDF) are comprehensively analyzed and provided data that are not available otherwise. The ceramic compositions correlate with the polymer compositions. The C-rich precursor forms C–C bonds through Si–O, Si–C, and C–H bond losses while less C-rich polymers have no significant C–C bond formation during C–H bond loss. The end structures have vastly different Si–O-rich and C-rich domain sizes, which cannot be observed by any bulk analysis. For the first time, H presence and cluster separation are shown to be determined by the polymer molecular structure. The RDF results show that higher pyrolysis temperature leads to more C–C bond formation. Even at 2100 K, C–H bonds are still prevalent and there is no long-range ordering. Such fundamental understanding provides new knowledge about polymer atomic evolution to silicon oxycarbide (SiOC) ceramics.

Bedree JK, Kerns K, Chen T, et al. Specific host metabolite and gut microbiome alterations are associated with bone loss during spaceflight. Cell Rep. 2023:112299. doi: 10.1016/j.celrep.2023.112299.

Understanding the axis of the human microbiome and physiological homeostasis is an essential task in managing deep-space-travel-associated health risks. The NASA-led Rodent Research 5 mission enabled an ancillary investigation of the gut microbiome, varying exposure to microgravity (flight) relative to ground controls in the context of previously shown bone mineral density (BMD) loss that was observed in these flight groups. We demonstrate elevated abundance of Lactobacillus murinus and Dorea sp. during microgravity exposure relative to ground control through whole-genome sequencing and 16S rRNA analyses. Specific functionally assigned gene clusters of L. murinus and Dorea sp. capable of producing metabolites, lactic acid, leucine/isoleucine, and glutathione are enriched. These metabolites are elevated in the microgravity-exposed host serum as shown by liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomic analysis. Along with BMD loss, ELISA reveals increases in osteocalcin and reductions in tartrate-resistant acid phosphatase 5b signifying additional loss of bone homeostasis in flight.

Aguilar M, Cavasonza LA, Ambrosi G, et al. Temporal structures in electron spectra and charge sign effects in galactic cosmic rays. Phys Rev Lett. 2023;130(16):161001. DOI: 10.1103/PhysRevLett.130.161001

We present the precision measurements of 11 years of daily cosmic electron fluxes in the rigidity interval from 1.00 to 41.9 GV based on 2.0×10^8 electrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The electron fluxes exhibit variations on multiple timescales. Recurrent electron flux variations with periods of 27 days, 13.5 days, and 9 days are observed. We find that the electron fluxes show distinctly different time variations from the proton fluxes. Remarkably, a hysteresis between the electron flux and the proton flux is observed with a significance of greater than 6σ at rigidities below 8.5 GV. Furthermore, significant structures in the electron-proton hysteresis are observed corresponding to sharp structures in both fluxes. This continuous daily electron data provide unique input to the understanding of the charge sign dependence of cosmic rays over an 11-year solar cycle.

Ghanbariamin, Delaram and Samandari, Mohamadmahdi and Ghelich, Pejman and Shahbazmohamadi, Sina and Schmidt, Tannin A. and Chen, Yupeng and Tamayol, Ali "Cleanroom-Free Fabrication of Microneedles for Multimodal Drug Delivery" Small , v.19 , 2023

Microneedles have recently emerged as a powerful tool for minimally invasive drug delivery and body fluid sampling. To date, high-resolution fabrication of microneedle arrays (MNAs) is mostly achieved by the utilization of sophisticated facilities and expertise. Particularly, hollow microneedles have usually been manufactured in cleanrooms out of silicon, resin, or metallic materials. Such strategies do not support the fabrication of microneedles from biocompatible/ biodegradable materials and limit the capability of multimodal drug delivery for the controlled release of different therapeutics through a combination of injection and sustained diffusion. This study implements low-cost 3D printers to fabricate relatively large needle arrays, followed by repeatable shrink-molding of hydrogels to form high-resolution molds for solid and hollow MNAs with controllable sizes. The developed strategy further enables modulating surface topography of MNAs to tailor their surface area and instantaneous wettability for controllable drug delivery and body fluid sampling. Hybrid gelatin methacryloyl (GelMA)/polyethylene glycol diacrylate (PEGDA) MNAs are fabricated using the developed strategy that can easily penetrate the skin and enable multimodal drug delivery. The proposed method holds promise for affordable, controllable, and scalable fabrication of MNAs by researchers and clinicians for controlled spatiotemporal administration of therapeutics and sample collection.

Perez, M. R., da Silva, V. A., Cortez, P. E., Joddar, B., & Willerth, S. M. (2023). 3D-bioprinted cardiac tissues and their potential for disease modeling. Journal of 3D printing in medicine, 7(3), 3DP6.

Heart diseases cause over 17.9 million total deaths globally, making them the leading source of mortality. The aim of this review is to describe the characteristic mechanical, chemical and cellular properties of human cardiac tissue and how these properties can be mimicked in 3D bioprinted tissues. Furthermore, the authors review how current healthy cardiac models are being 3D bioprinted using extrusion-, laser- and inkjet-based printers. The review then discusses the pathologies of cardiac diseases and how bioprinting could be used to fabricate models to study these diseases and potentially find new drug targets for such diseases. Finally, the challenges and future directions of cardiac disease modeling using 3D bioprinting techniques are explored.

El Khoury, R., Ramirez, S. P., Loyola, C. D., & Joddar, B. (2023). Demonstration of doxorubicin's cardiotoxicity and screening using a 3D bioprinted spheroidal droplet-based system. RSC advances, 13(12), 8338-8351.

Doxorubicin (DOX) is a highly effective anthracycline chemotherapy agent effective in treating a broad range of life-threatening malignancies but it causes cardiotoxicity in many subjects. While the mechanism of its cardiotoxic effects remains elusive, DOX-related cardiotoxicity can lead to heart failure in patients. In this study, we investigated the effects of DOX-induced cardiotoxicity on human cardiomyocytes (CMs) using a three-dimensional (3D) bioprinted cardiac spheroidal droplet based-system in comparison with the traditional two-dimensional cell (2D) culture model. The effects of DOX were alleviated with the addition of N-acetylcysteine (NAC) and Tiron. Caspase-3 activity was quantified, and reactive oxygen species (ROS) production was measured using dihydroethidium (DHE) staining. Application of varying concentrations of DOX (0.4 μM–1 μM) to CMs revealed a dose-specific response, with 1 μM concentration imposing maximum cytotoxicity and 0.22 ± 0.11% of viable cells in 3D samples versus 1.02 ± 0.28% viable cells in 2D cultures, after 5 days of culture. Moreover, a flow cytometric analysis study was conducted to study CMs proliferation in the presence of DOX and antioxidants. Our data support the use of a 3D bioprinted cardiac spheroidal droplet as a robust and high-throughput screening model for drug toxicity. In the future, this 3D spheroidal droplet model can be adopted as a human-derived tissue-engineered equivalent to address challenges in other various aspects of biomedical pre-clinical research.

Joddar, B., Loyola, C. D., Ramirez, S. P., Muruganandham, A., & Singh, I. (2023). Inhibition of ERK 1/2 pathway downregulates YAP1/TAZ signaling in human cardiomyocytes exposed to hyperglycemic conditions. Biochemical and Biophysical Research Communications, 648, 72-80.

Hyperglycemia-mediated cardiac dysfunction is an acute initiator in the development of vascular complications, leading to cardiac fibrosis. To investigate the effects of hyperglycemia-mediated changes in cardiomyocytes, cells were cultured in-vitro under normoglycemic (5 mM or 25 mM D-glucose) and hyperglycemic (5 → 50 mM or 25 → 50 mM D-glucose) conditions, respectively. After 24-h of hyperglycemic exposure, cells were collected for RNA-sequencing (RNA-seq) studies to further investigate the differentially expressed genes (DEG) related to inflammation and fibrosis in samples cultured under hyperglycemic-in comparison with normoglycemic-conditions. Western Blotting was done to evaluate the protein expression of YAP1/TAZ under hyperglycemia induced stress conditions, as it is known to be involved in fibrotic and vascular inflammatory-mediated conditions. RNA-seq revealed the DEG of multiple targets including matrix metalloproteinases and inflammatory mediators, whose expression was significantly altered in the 5 → 50 mM in comparison with the 25 → 50 mM condition. Western Blotting showed a significant upregulation of the protein expression of the YAP1/TAZ pathway under these conditions as well (5 → 50 mM). To further probe the relationship between the inflammatory extracellular-signal-regulated kinase (ERK 1/2) and its downstream effects on YAP1/TAZ expression we studied the effect of inhibition of the ERK 1/2 signaling cascade in the 5 → 50 mM condition. The application of an ERK 1/2 inhibitor inhibited the expression of the YAP1/TAZ protein in the 5 → 50 mM condition, and this strategy may be useful in preventing and improving hyperglycemia associated cardiovascular damage and inflammation.

Ganesh SC, Koplik J, Morris JF, Maldarelli C. Dynamics of a surface tension driven colloidal motor based on an active Janus particle encapsulated in a liquid drop. Journal of Fluid Mechanics. 2023;958:A12. https://doi.org/10.1017/jfm.2023.5

A colloidal motor driven by surface tension forces is theoretically designed by encapsulating an active Janus particle in a liquid drop which is immiscible in the suspending medium. The Janus particle produces an asymmetric flux of a solute species which induces surface tension gradients along the liquid–liquid interface between the drop and the surrounding fluid. The resulting Marangoni forces at the interface propel the compound drop/Janus particle system. The propulsion speeds of the motor are evaluated for a range of relative sizes and positions of the drop and the particle and across a range of transport properties of the drop and the suspending medium. It is demonstrated that the proposed design can produce higher propulsion velocities than the traditional Janus-particle-based colloidal motors propelled by neutral diffusiophoresis.

Dinesh B, Livesay J, Ignatius IB, Narayanan R. Pattern formation in Faraday instability—experimental validation of theoretical models. Philosophical Transactions Royal Society A. 2023:381;20220081.

Two types of resonance-derived interfacial instability are reviewed with a focus on recent work detailing the effect of side walls on interfacial mode discretization. The first type of resonance is the mechanical Faraday instability, and the second is electrostatic Faraday instability. Both types of resonance are discussed for the case of single-frequency forcing. In the case of mechanical Faraday instability, inviscid theory can forecast the modal forms that one might expect when viscosity is taken into account. Experiments show very favourable validation with theory for both modal forms and onset conditions. Lowering of gravity is predicted to shift smaller wavelengths or choppier modes to lower frequencies. This is also validated by experiments. Electrostatic resonant instability is shown to lead to a pillaring mode that occurs at low wavenumbers, which is akin to Rayleigh Taylor instability. As in the case of mechanical resonance, experiments show favourable validation with theoretical predictions of patterns. A stark difference between the two forms of resonance is the observation of a gradual rise in the negative detuning instability in the case of mechanical Faraday and a very sharp one in the case of electrostatic resonance.

Hwang, Hyun and Liu, Rui and Eldridge, Ronald and Hu, Xin and Forghani, Parvin and Jones, Dean P. and Xu, Chunhui "Chronic ethanol exposure induces mitochondrial dysfunction and alters gene expression and metabolism in human cardiac spheroids" Alcohol: Clinical and Experimental Research , v.47 , 2023

Background Chronic alcohol consumption in adults can induce various cardiac toxicities such as arrhythmias, cardiomyopathy, and heart failure. Prenatal alcohol exposure can increase the risk of developing congenital heart defects among offspring. Understanding the molecular mechanisms underlying long-term alcohol exposure-induced cardiotoxicity can help guide the development of therapeutic strategies. Methods Cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) were engineered into cardiac spheroids and treated with clinically relevant concentrations of ethanol (17 and 50 mM) for 5 weeks. The cells were then analyzed for changes in mitochondrial features, transcriptomic and metabolomic profiles, and integrated omics outcomes. Results Following chronic ethanol treatment of hiPSC-CMs, a decrease in mitochondrial membrane potential and respiration and changes in expression of mitochondrial function-related genes were observed. RNA-sequencing analysis revealed changes in various metabolic processes, heart development, response to hypoxia, and extracellular matrix-related activities. Metabolomic analysis revealed dysregulation of energy metabolism and increased metabolites associated with the upregulation of inflammation. Integrated omics analysis further identified functional subclusters and revealed potentially affected pathways associated with cardiac toxicities. Conclusion Chronic ethanol treatment of hiPSC-CMs resulted in overall decreased mitochondrial function, increased glycolysis, disrupted fatty acid oxidation, and impaired cardiac structural development.

Vagelli V, Graziani M. The AMS-02 detector on the ISS - Status and highlights after 11 years on orbit. J Phys Conf Series. 2023; 2429:012002. doi: 10.1088/1742-6596/2429/1/012002

The Alpha Magnetic Spectrometer, AMS-02, is a magnetic spectrometer detector operating on the International Space Station (ISS) since May the 19th, 2011. More than 200 billion events have been collected by the instrument in the first 11 years of data taking, providing detailed and novel insights on the composition and energy spectra of cosmic rays up to TeV energies. We review the most recent AMS-02 measurements and the advances in the understanding of cosmic ray origin, acceleration and propagation physics.